Regulation of bone mass at unloaded condition by osteocyte network

Excerpt

Disuse osteoporosis, which occurs commonly in prolonged bed rest and immobilization, is becoming a major problem in modern societies; however, the molecular mechanisms underlying unloading-driven bone loss have not been fully elucidated. Bone adjusts its shape and strength against mechanical stress. Osteocytes are the most abundant cells in bone and comprise the communication system through the processes and canaliculi throughout bone. The osteocyte network is considered to be an ideal mechanosensor and mechanotransduction system. We found that overexpression of BCL2 in osteoblasts reduces the number of osteocyte processes, probably due to the function of Bcl2 that modulates cytoskeletal reorganization, and induces the apoptosis of osteocytes, in which the transgene expression was reduced, presumably caused by an insufficient supply of oxygen, nutrients, and survival factors due to the reduced osteocyte processes. Our BCL2 transgenic mouse with accumulated dead osteocytes is a useful model to analyze the function of osteocytes, because a repair process, which replaces dead osteocytes with new osteocytes by bone resorption and formation, was not evident in the mice irrespective of the massive accumulation of dead osteocytes …